TY - JOUR
T1 - The immune cell landscape in kidneys of patients with lupus nephritis
AU - the Accelerating Medicines Partnership in SLE network
AU - Arazi, Arnon
AU - Rao, Deepak A.
AU - Berthier, Celine C.
AU - Davidson, Anne
AU - Liu, Yanyan
AU - Hoover, Paul J.
AU - Chicoine, Adam
AU - Eisenhaure, Thomas M.
AU - Jonsson, A. Helena
AU - Li, Shuqiang
AU - Lieb, David J.
AU - Zhang, Fan
AU - Slowikowski, Kamil
AU - Browne, Edward P.
AU - Noma, Akiko
AU - Sutherby, Danielle
AU - Steelman, Scott
AU - Smilek, Dawn E.
AU - Tosta, Patti
AU - Apruzzese, William
AU - Massarotti, Elena
AU - Dall’Era, Maria
AU - Park, Meyeon
AU - Kamen, Diane L.
AU - Furie, Richard A.
AU - Payan-Schober, Fernanda
AU - Pendergraft, William F.
AU - McInnis, Elizabeth A.
AU - Buyon, Jill P.
AU - Petri, Michelle A.
AU - Putterman, Chaim
AU - Kalunian, Kenneth C.
AU - Woodle, E. Steve
AU - Lederer, James A.
AU - Hildeman, David A.
AU - Nusbaum, Chad
AU - Raychaudhuri, Soumya
AU - Kretzler, Matthias
AU - Anolik, Jennifer H.
AU - Brenner, Michael B.
AU - Wofsy, David
AU - Hacohen, Nir
AU - Diamond, Betty
AU - Waguespack, Dia
AU - Connery, Sean M.
AU - McMahon, Maureen A.
AU - McCune, William J.
AU - Kado, Ruba B.
AU - Hsu, Raymond
AU - Cunningham, Melissa A.
N1 - Publisher Copyright:
© 2019, The Author(s), under exclusive licence to Springer Nature America, Inc.
PY - 2019/7/1
Y1 - 2019/7/1
N2 - Lupus nephritis is a potentially fatal autoimmune disease for which the current treatment is ineffective and often toxic. To develop mechanistic hypotheses of disease, we analyzed kidney samples from patients with lupus nephritis and from healthy control subjects using single-cell RNA sequencing. Our analysis revealed 21 subsets of leukocytes active in disease, including multiple populations of myeloid cells, T cells, natural killer cells and B cells that demonstrated both pro-inflammatory responses and inflammation-resolving responses. We found evidence of local activation of B cells correlated with an age-associated B-cell signature and evidence of progressive stages of monocyte differentiation within the kidney. A clear interferon response was observed in most cells. Two chemokine receptors, CXCR4 and CX3CR1, were broadly expressed, implying a potentially central role in cell trafficking. Gene expression of immune cells in urine and kidney was highly correlated, which would suggest that urine might serve as a surrogate for kidney biopsies.
AB - Lupus nephritis is a potentially fatal autoimmune disease for which the current treatment is ineffective and often toxic. To develop mechanistic hypotheses of disease, we analyzed kidney samples from patients with lupus nephritis and from healthy control subjects using single-cell RNA sequencing. Our analysis revealed 21 subsets of leukocytes active in disease, including multiple populations of myeloid cells, T cells, natural killer cells and B cells that demonstrated both pro-inflammatory responses and inflammation-resolving responses. We found evidence of local activation of B cells correlated with an age-associated B-cell signature and evidence of progressive stages of monocyte differentiation within the kidney. A clear interferon response was observed in most cells. Two chemokine receptors, CXCR4 and CX3CR1, were broadly expressed, implying a potentially central role in cell trafficking. Gene expression of immune cells in urine and kidney was highly correlated, which would suggest that urine might serve as a surrogate for kidney biopsies.
UR - http://www.scopus.com/inward/record.url?scp=85067631551&partnerID=8YFLogxK
U2 - 10.1038/s41590-019-0398-x
DO - 10.1038/s41590-019-0398-x
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C2 - 31209404
AN - SCOPUS:85067631551
SN - 1529-2908
VL - 20
SP - 902
EP - 914
JO - Nature Immunology
JF - Nature Immunology
IS - 7
ER -